The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders.DOI: http://dx.doi.org/10.7554/eLife.17197.001
While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. Prior studies have found that cortical thickness in the cingulate cortex, a region involved in information processing, memory, and attention, distinguish those with exceptional cognitive abilities when compared to their cognitively more typical elderly peers. Others major areas outside of the cingulate, such as the prefrontal cortex and insula, are also key in successful aging well into late age, suggesting that structural properties across a wide range of areas may better explain differences in cognitive abilities. Here, we aim to assess the role of regional cortical thickness, both in the cingulate and the whole brain, in modeling Top Cognitive Performance (TCP), measured by performance in the top 50th percentile of memory and executive function. Using data from National Alzheimer’s Coordinating Center and The 90 + Study, we examined healthy subjects aged 70–100 years old. We found that, while thickness in cingulate regions can model TCP status with some degree of accuracy, a whole-brain, network-level approach out-performed the localist, cingulate models. These findings suggests a need for more network-style approaches and furthers our understanding of neurobiological factors contributing to preserved cognition.
Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling leads to memory deficits and abnormal social behaviors in adults. However, whether mTORC1 is involved in critical periods of early learning remains largely unexplored. Our study addressed this question by investigating imprinting, a form of learning constrained to a sensitive period that supports filial attachment, in newborn chickens. Imprinting to virtual objects and sounds was assessed after acute manipulations of mTORC1. To further understand the role of mTORC1 during the critical period, structural plasticity was analyzed using DiOlistic labeling of dendritic spines. We found that mTORC1 is required for the emergence of experience-dependent preferences and structural plasticity within brain regions controlling behavior. Furthermore, upon critical period closure, pharmacological activation of the AKT/mTORC1 pathway was sufficient to rescue imprinting across sensory modalities. Thus, our results uncover a novel role of mTORC1 in the formation of imprinted memories and experience-dependent reorganization of neural circuits during a critical period.
Background SuperAgers are individuals who, despite their advanced age, retain superior cognitive performance. Although there is no consensus on how to define SuperAgers, identifying such individuals remains an important research question as they may help us identify protective factors against cognitive impairment that may be amenable to intervention strategies. Here we explore whether ‘SuperAgers’ who are the best performers in a test of memory, show equally exceptional performance in other cognitive domains. Method Participants are from The 90+ Study, a longitudinal study of aging and dementia in people 90 and older. Out of 1,134 participants in the study, the 349 with normal cognition at baseline were included in these analyses. Cognitive diagnosis was based on clinical examination and mental status exam independent of the tests investigated here. We evaluated performance in tests of verbal memory (9‐item California Verbal Learning Test‐long delay [CVLT]), executive function (Trails B), language (15‐item Boston naming test [BNT]), and attention (Digit Span backward [DSB]). For each test, we determined whether participants were in the top quartile of performance (SuperAgers). We investigated whether SuperAgers according to memory were also SuperAgers in other domains. We also tested whether being a SuperAger was related to age, sex, or education. Result 47 participants were in the top quartile of CVLT with a perfect score of 9 and were classified as memory‐SuperAgers. Of these 47 participants, 8 (17%) were also in the top quartile for Trails B, 14 (30%) in the top quartile for BNT, and 12 (26%) in the top quartile of DSB (Figure). None of the 349 participants were in the top quartile for all four tests and only 13 participants (4%) were in the top quartile for three tests (Figure). Younger age was associated with being a SuperAger for CVLT, Trails B, & BNT and female sex was associated with being a memory‐SuperAger (CVLT) (Table). Education was not associated with being a SuperAger for any test. Conclusion In this oldest‐old cohort, those who perform exceptionally well in a memory test do not perform equally well in other cognitive tests suggesting that the biological and sociodemographic determinants of superior performance will vary by cognitive domain.
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